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Multi-modal Assessment of Gamma-aminobutyric Acid (GABA) Function in Psychosis (GABAmech)

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ClinicalTrials.gov Identifier: NCT04004416
Recruitment Status : Not yet recruiting
First Posted : July 2, 2019
Last Update Posted : July 2, 2019
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Stephan Taylor, University of Michigan

Brief Summary:

The purpose of this study is to better understand mental illness and will test the hypotheses that while viewing affective stimuli, patient groups will show increased blood oxygenation level dependent (BOLD) signal by fMRI after lorazepam.

This study will enroll participants between the ages of 16 and 60, who have a psychotic illness (such as schizophrenia, bipolar disorder, and schizoaffective disorder. The study will also enroll eligible participants without any psychiatric illness, to compare their brains.

The study will require participants to have 3-4 sessions over a few weeks. The first session (may be over two visits) will include a diagnostic interview and several questionnaires (qols) to assess eligibility. Subsequently, there will will be two separate functional magnetic resonance imaging (fMRI) sessions in which lorazepam or placebo will be given prior to the MRI. During the fMRI the participants will also be asked to answer questions. Additionally, the participants will have their blood drawn, women of child bearing potential will have a urine pregnancy test, vital signs taken, and asked to complete more qols.


Condition or disease Intervention/treatment Phase
Schizophrenia Bipolar Disorder Healthy Psychosis Schizophreniform Disorders Schizo Affective Disorder Other: Placebo and fMRI Drug: Lorazepam and fMRI Phase 4

Detailed Description:
Please note the collaborator (NIMH) is requesting that an NCT number be obtained prior to receiving the award number.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 232 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: The two MRI sessions will will be scheduled about 1 week apart. If you are a woman, we may need to schedule the scanning session to coincide with a certain phase of your menstrual cycle.
Masking: Single (Participant)
Primary Purpose: Basic Science
Official Title: Multi-modal Assessment of GABA Function in Psychosis
Estimated Study Start Date : November 2019
Estimated Primary Completion Date : March 2024
Estimated Study Completion Date : September 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Lorazepam

Arm Intervention/treatment
Placebo Comparator: Healthy Controls Other: Placebo and fMRI
A dose of Placebo will be given 90 minutes prior to entering the fMRI scanner. At each visit volunteers will complete assessments (blood draw, vitals, qols) prior to having an fMRI. Females may need to have this scheduled to coincide with a certain phase of their menstrual cycle. During the fMRI participants will be asked to view pleasant/unpleasant pictures and rate them while you are inside the scanner.
Other Name: inactive medication

Drug: Lorazepam and fMRI
A dose of Lorazepam (assigned to one of two dose levels between subjects: 0.01 mg/kg or 0.02 mg/kg) will be given 90 minutes prior to entering the fMRI scanner. At each visit volunteers will complete assessments (blood draw, vitals, qols) prior to having an fMRI. There will be two fMRIs done approximately 1 week apart and after the assessment visit. Females may need to have this scheduled to coincide with a certain phase of their menstrual cycle. During the fMRI participants will be asked to view pleasant/unpleasant pictures and rate them while you are inside the scanner.
Other Name: Ativan

Experimental: Early Psychosis patients Other: Placebo and fMRI
A dose of Placebo will be given 90 minutes prior to entering the fMRI scanner. At each visit volunteers will complete assessments (blood draw, vitals, qols) prior to having an fMRI. Females may need to have this scheduled to coincide with a certain phase of their menstrual cycle. During the fMRI participants will be asked to view pleasant/unpleasant pictures and rate them while you are inside the scanner.
Other Name: inactive medication

Drug: Lorazepam and fMRI
A dose of Lorazepam (assigned to one of two dose levels between subjects: 0.01 mg/kg or 0.02 mg/kg) will be given 90 minutes prior to entering the fMRI scanner. At each visit volunteers will complete assessments (blood draw, vitals, qols) prior to having an fMRI. There will be two fMRIs done approximately 1 week apart and after the assessment visit. Females may need to have this scheduled to coincide with a certain phase of their menstrual cycle. During the fMRI participants will be asked to view pleasant/unpleasant pictures and rate them while you are inside the scanner.
Other Name: Ativan

Experimental: Schizophrenia or Schizoaffective disorder patients Other: Placebo and fMRI
A dose of Placebo will be given 90 minutes prior to entering the fMRI scanner. At each visit volunteers will complete assessments (blood draw, vitals, qols) prior to having an fMRI. Females may need to have this scheduled to coincide with a certain phase of their menstrual cycle. During the fMRI participants will be asked to view pleasant/unpleasant pictures and rate them while you are inside the scanner.
Other Name: inactive medication

Drug: Lorazepam and fMRI
A dose of Lorazepam (assigned to one of two dose levels between subjects: 0.01 mg/kg or 0.02 mg/kg) will be given 90 minutes prior to entering the fMRI scanner. At each visit volunteers will complete assessments (blood draw, vitals, qols) prior to having an fMRI. There will be two fMRIs done approximately 1 week apart and after the assessment visit. Females may need to have this scheduled to coincide with a certain phase of their menstrual cycle. During the fMRI participants will be asked to view pleasant/unpleasant pictures and rate them while you are inside the scanner.
Other Name: Ativan

Experimental: Bipolar disorder patients Other: Placebo and fMRI
A dose of Placebo will be given 90 minutes prior to entering the fMRI scanner. At each visit volunteers will complete assessments (blood draw, vitals, qols) prior to having an fMRI. Females may need to have this scheduled to coincide with a certain phase of their menstrual cycle. During the fMRI participants will be asked to view pleasant/unpleasant pictures and rate them while you are inside the scanner.
Other Name: inactive medication

Drug: Lorazepam and fMRI
A dose of Lorazepam (assigned to one of two dose levels between subjects: 0.01 mg/kg or 0.02 mg/kg) will be given 90 minutes prior to entering the fMRI scanner. At each visit volunteers will complete assessments (blood draw, vitals, qols) prior to having an fMRI. There will be two fMRIs done approximately 1 week apart and after the assessment visit. Females may need to have this scheduled to coincide with a certain phase of their menstrual cycle. During the fMRI participants will be asked to view pleasant/unpleasant pictures and rate them while you are inside the scanner.
Other Name: Ativan




Primary Outcome Measures :
  1. Blood Oxygen level dependent (BOLD) in medial frontal cortex while viewing affective pictures [ Time Frame: 2 hours after ingestion of lorazepam/placebo ]
    BOLD signal change in medial frontal cortex after lorazepam challenge during fMRI



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   16 Years to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Early psychosis (EP) patients:

Inclusion Criteria:

  • Meets Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for schizophrenia, schizophreniform disorder, schizoaffective disorder, bipolar disorder type 1, with history of psychosis, or other specified/unspecified psychotic disorder; or, meets Structured Interview for Psychosis Syndromes (SIPS) criteria for Presence of Psychotic Symptoms or Brief Intermittent Psychotic Syndrome (BIPS)
  • Ability and willingness to give informed consent to participate;
  • 16-25 years old
  • Positive symptom onset ≤ 2 years
  • No history of active substance use disorder in the past 2 months
  • Not currently on an involuntary treatment order
  • Not taking chronic narcotics, barbiturates, benzodiazepines
  • Absence of suicidal thoughts with plans or intentions, as assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)
  • No changes in psychotropic medication within the prior 4 weeks and for half of EP sample, or not taking antipsychotic medication within the prior 4 weeks. Patients may take as needed doses of benzodiazepines as clinically prescribed, as long as those doses are not required within 5 half-lives of an MRI session
  • Ability to tolerate small, enclosed spaces without anxiety
  • No metals, implants or metallic substances within or on the body that might cause adverse effects to the subject in a strong magnetic field, or interfere with image acquisition, e. g. aneurysm clips, retained particles (metal workers excluded), neurostimulators, foil-backed transdermal patches, carotid or cerebral stents, cerebral spinal fluid (CSF)shunts; magnetic dental implants, ferromagnetic ocular implants, pacemakers, automatic implantable defibrillators
  • Size compatible with scanner gantry, e. g. men over 6 feet tall that weigh more than 250 pounds (lbs), men under 6 feet tall that weigh over 220 lbs, women over 5'11" tall that weigh more than 220 lbs, or women under 5'10" tall that weigh more than 200 lbs. Subjects of these weights or greater typically have difficult fitting into the fMRI scanner properly.

Exclusion:

  • If a woman of child bearing age, not pregnant or trying to become pregnant
  • History of serious neurological illness or current medical condition that could compromise brain function, such as liver failure
  • History of closed head injury, for example (e.g.) loss of consciousness > ~5 min, hospitalization, neurological sequela

Schizophrenia/schizoaffective and bipolar disorder patients

Inclusion Criteria:

  • Ability and willingness to give informed consent to participate;
  • 16- 60 years old
  • Meets DSM- 5 criteria for schizophrenia, or schizoaffective disorder (SCZ), or bipolar disorder type 1, with history of psychosis bipolar affective disorder (BAD)
  • Duration of positive symptom onset > 2 years
  • No history of active substance use disorder in the past 2 months
  • Not currently on an involuntary treatment order
  • Not taking chronic narcotics, barbiturates, benzodiazepines
  • Absence of suicidal thoughts with plans or intentions, as assessed by C-SSRS
  • No changes in psychotropic medication within the prior 4 weeks. Patients may take as needed doses of benzodiazepines as clinically prescribed, as long as those doses are not required within 5 half-lives of an MRI session
  • Ability to tolerate small, enclosed spaces without anxiety
  • No metals, implants or metallic substances within or on the body that might cause adverse effects to the subject in a strong magnetic field, or interfere with image acquisition, e. g. aneurysm clips, retained particles (metal workers excluded), neurostimulators, foil-backed transdermal patches, carotid or cerebral stents, CSF shunts; magnetic dental implants, ferromagnetic ocular implants, pacemakers, automatic implantable defibrillators
  • Size compatible with scanner gantry, e. g. men over 6 feet tall that weigh more than 250 lbs, men under 6 feet tall that weigh over 220 lbs, women over 5'11" tall that weigh more than 220 lbs, or women under 5'10" tall that weigh more than 200 lbs. Subjects of these weights or greater typically have difficult fitting into the fMRI scanner properly.

Exclusion:

  • If a woman of child bearing age, not pregnant or trying to become pregnant
  • History of serious neurological illness or current medical condition that could compromise brain function, such as liver failure
  • History of closed head injury, for example (e.g.) loss of consciousness > ~5 min, hospitalization, neurological sequela

Healthy control subjects:

Inclusion Criteria:

  • Ability and willingness to give informed consent to participate
  • Age 16 - 60
  • No history of (h/o) past or current mental illness (except for simple phobias), but prior h/o substance abuse ok if in remission for greater than 5 years
  • Not taking any medication, prescription or non-prescription, with psychotropic effects (birth control medications allowed)
  • No first-degree family members with a history of a psychotic disorder (including bipolar disorder)
  • Ability to tolerate small, enclosed spaces without anxiety
  • No metals, implants or metallic substances within or on the body that might cause adverse effects to the subject in a strong magnetic field, or interfere with image acquisition, e. g. aneurysm clips, retained particles (metal workers excluded), neurostimulators, foil-backed transdermal patches, carotid or cerebral stents, CSF shunts; magnetic dental implants, ferromagnetic ocular implants, pacemakers, automatic implantable defibrillators
  • Size compatible with scanner gantry, e. g. men over 6 feet tall that weigh more than 250 lbs, men under 6 feet tall that weigh over 220 lbs, women over 5'11" tall that weigh more than 220 lbs, or women under 5'10" tall that weigh more than 200 lbs. Subjects of these weights or greater typically have difficult fitting into the fMRI scanner properly.

Exclusion:

  • If a woman of child bearing age, not pregnant or trying to become pregnant
  • History of serious neurological illness or current medical condition that could compromise brain function, such as liver failure
  • History of closed head injury, for example (e.g.) loss of consciousness > ~5 min, hospitalization, neurological sequela

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04004416


Contacts
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Contact: laura Stchur, MSW 734-936-1323 lmarine@med.umich.edu

Locations
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United States, Michigan
University of Michigan Not yet recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Laura Stchur, MSW    734-936-1323    lmarine@med.umich.edu   
Principal Investigator: Stephan Taylor, MD         
Sponsors and Collaborators
University of Michigan
National Institute of Mental Health (NIMH)
Investigators
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Principal Investigator: Stephan Taylor, MD University of Michigan

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Responsible Party: Stephan Taylor, Professor of Psychiatry, University of Michigan
ClinicalTrials.gov Identifier: NCT04004416     History of Changes
Other Study ID Numbers: HUM00162597
First Posted: July 2, 2019    Key Record Dates
Last Update Posted: July 2, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

The PI will share information about this/these trial(s) via timely registration, updates, and results reporting in ClinicalTrials.gov in accordance with NIH policy.

The PI will also upload data gathered in this proposal to an National Institute of Mental Health (NIMH)-designated central data, NIMH Data Archive (NDA), as prescribed by NOT-MH-15-012, working with NIMH program to determine the timing and extent of data sharing. This includes formulation of an enrollment strategy that will obtain the information necessary to generate a Global Unique Identifier (GUID) for each participant.

The consent form will include language indicating the intention to upload de-identified data into the central archive, and permission will be obtained from University of Michigan Institutional Review Board to do so. The budget includes a data manager to cover the costs of managing the data, building the data dictionary and harmonizing it with data structures.

Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: De-identified data will be entered into the NDA within 1 year of the conclusion of the study.
Access Criteria: No additional access restrictions will be placed on the de-identified data beyond those that are standard for the NDA.
URL: https://nda.nih.gov

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Disease
Schizophrenia
Bipolar Disorder
Psychotic Disorders
Mental Disorders
Mood Disorders
Pathologic Processes
Schizophrenia Spectrum and Other Psychotic Disorders
Bipolar and Related Disorders
Lorazepam
Anticonvulsants
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hypnotics and Sedatives
Central Nervous System Depressants
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action